Case Report

Improvement of Renal Function after Opening Occluded Atherosclerotic Renal Arteries

*Hiroshi Kanamori, MD, PhD, §Masanao Toma, MD, *Atsushi Fukatsu, MD, PhD
*Hiroshi Kanamori, MD, PhD, §Masanao Toma, MD, *Atsushi Fukatsu, MD, PhD
From the *Department of Nephrology, Kyoto University Graduate School of Medicine, and the §Department of Cardiovascular Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan. The authors report no conflicts of interest regarding the content herein. Manuscript submitted February 27, 2009, provisional acceptance given April 13, 2009, and final version accepted April 17, 2009. Address for correspondence: Hiroshi Kanamori, MD, PhD, Department of Nephrology, Kyoto University Graduate School of Medicine, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto, 606-8507, Japan. E-mail: h-kanamori@live.jp

_______________________________________________ ABSTRACT: Percutaneous transluminal renal angioplasty (PTRA) with stenting has been effective in the control of hypertension, renal function and pulmonary edema caused by atherosclerotic renal artery stenosis (ARAS). However, concerning the viability of renal function, this procedure has not been fully established, especially in the presence of renal atrophy or severe renal parenchymal disease. We report a dramatically improved case of acute renal failure caused by acute worsening ARAS treated by stenting. A 72-year-old female was admitted for accelerated renal dysfunction (serum ceatinine; 1.2–2.3 mg/dl) and hypertension (190/100 mmHg). At 10 days after admission, the patient’s serum ceatinine increased to 6.7 mg/dl, her pulmonary edema was exaggerated and hemodialysis was required. Ultrasonography showed bilateral high-echoic kidneys, but no apparent finding of renal artery stenosis (RAS). At day 15, computed tomographic angiography indicated bilateral ostial RAS. Renal angiography demonstrated total occlusion of the right and severe (90%) disease in the left. ARAS was diagnosed by intravascular ultrasonography. The guidewire was inserted in both renal arteries, PTRA with stenting was performed in the right and a stent was directly implanted in the left. Immediately, each kidney enlarged to almost normal size, leading to satisfactory urination. She was released from hemodialysis the next day since her serum creatinine was normal and the pulmonary edema was improved. Although there is still no reliable prognostic factor including resistive index or kidney size, it is important that PTRA with stenting in ARAS should be considered in a case of accelerated renal dysfunction because of the possible improvement.

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J INVASIVE CARDIOL 2009;21:E171–E174 It is well known that renal artery stenosis causes refractory hypertension. Among the diseases that cause renal artery stenosis, including atherosclerotic renal artery stenosis (ARAS), fibromuscular dysplasia (FMD), aortic dissection, aortitis, and so on, ARAS is the most common underlying cause (approximately 90%).1 Recently, noninvasive diagnostic techniques have been established for the examination of renal arteries including magnetic resonance angiography (MRA), computed tomographic angiography (CTA), and duplex ultrasonography, and ARAS has begun to draw attention as the cause of end-stage renal disease (ESRD).2 It is reported that early identification and management of ARAS, especially percutaneous renal angioplasty (PTRA) followed by primary stenting, have a beneficial effect on the control of hypertension and renal function.3 However, concerning the viability of renal function, this procedure has not been established, especially in the presence of renal atrophy or severe renal parenchymal disease.4,5 Here we report a dramatically improved case of acute renal failure caused by possible acute worsening ARAS (total occlusion in the right renal artery and 90% stenosis in left) and treated by intravascular stent placement with or without PTRA. This case offers some clues to the appropriate indication for PTRA and stenting to treat ARAS. Case Description. We present a case of acute renal failure with bilateral severe ARAS treated by PTRA followed by intravascular stent placement, leading to the discontinuation of hemodialysis (HD). A 72-year-old female presented with dizziness associated with hypertension (190/100 mmHg), and candesartan (8 mg) was administered. Laboratory findings showed renal dysfunction (sCr, 1.2 mg/dl). Twenty days later, the patient’s serum creatinine had increased to 2.3 mg/dl and her hypertension had not improved. She was therefore admitted to our hospital for further examination. Since her renal functional decline appeared to be due to angiotensin receptor-blockers (ARB), which implied the existence of bilateral ARAS, nifedipine (40 mg) was administered as a substitute for candesartan on admission (day-0). Urine analysis showed no apparent abnormal finding. A bruit was heard beside the umbilicus. At day-10, the patient’s urinary volume declined and her serum creatinine had increased to 6.7 mg/dl. Although furosemide was administered, her pulmonary edema was exaggerated (Figure 1A) and HD was required. The patient’s plasma rennin activity (PRA) and serum aldosterone6 level were revealed to be high (PRA 17.3 ng/ml/hour; Ald 402 pg/ml) (Table 1). Renal artery stenosis was suspected, however, no clear finding was confirmed with duplex ultrasonography (Table 1). Renal echography showed atrophic kidneys. These facts implied that both kidneys might not viable. However, we decided to perform an interventional study because the patient’s clinical course was acute and there was a possibility of recovering renal function. At day-15, CT angiography showed bilateral ostial renal artery stenosis and atrophic kidneys (long-axis: right 74 mm; left 85 mm) (Figure 2). Renal angiography demonstrated total occlusion of the right renal artery and severe (90%) disease in the left renal artery (Figures 3A and 3E, respectively). ARAS was diagnosed for its plaque formation by intravascular ultrasonography (IVUS). The totally occluded lesion of right renal artery was successfully crossed and was dilated using a 2.0 balloon catheter and a Genesis 4.0 x 18 mm stent was implanted with IVUS guidance, followed by dilatation using 3.5 and 4.0 mm balloon catheters (Figures 3B and 3C). Final angiography showed 0% residual stenosis with normal flow (Figure 3D). A Genesis 5.0 x 18 mm stent was directly implanted in the left renal artery without predilatation (Figures 3 E and F). Immediately after the revascularization of the renal arteries, both kidneys were enlarged to almost normal size. Sufficient urination was noticed during the intervention. The patient was released from HD. Her serum creatinine and PRA normalized to 0.8 mg/dl and 0.7 ng/ml/hr, respectively. Her pulmonary edema was completely ameliorated (Figure 1B). The patient’s hypertension also improved to 140/90 mmHg. Discussion. ARAS is the most common underlying cause of renal artery stenosis.1 Advanced age, hyperlipidemia, diabetes mellitus, smoking, heart disease and vascular disease are cited as risk factors.6 Our case did not have any apparent risk factors except a slightly high level of serum total cholesterol and advanced age. However, severe atherosclerotic lesions in bilateral renal arteries were diagnosed by IVUS. The most crucial clinical findings associated with ARAS are hypertension and renal dysfunction. Hypertension is due to the activation of the rennin-angiotensin pathway,7 which usually worsens rapidly refractory to antihypertensive agents. Renal dysfunction is caused by ischemic nephropathy, with renal parenchymal ischemia caused by a decrement of renal perfusion, often developing into end-stage renal disease (ESRD) and requiring dialysis therapy.8 Although angiography is historically the gold standard for diagnosing renal artery stenosis, it may cause atheroembolism and contrast nephropathy. Recently, various noninvasive methods such as MRA, CTA and duplex ultrasonography have been devised and developed. Although MRA and CTA are equal to angiography in terms of sensitivity and specificity (MRA: approximately 90–95%, CTA: approximately 95%), CTA poses a risk of contrast nephropathy, and MRA poses a risk of gadolinium-induced nephrogenic systemic fibrosis.9 Taking those facts into consideration, duplex ultrasonography is the safest and most convenient on a cost/performance basis. Although the usefulness of duplex ultrasonography depends on the technical skill of the operator, it was recently reported that its sensitivity and specificity are 90–95%.10,11 Duplex ultrasonography can provide information about the viability of kidneys with ARAS. According to Strandness et al, both a peak systolic velocity (PSV) of a renal artery > 180 cm/sec and a renal-to-aorta ratio (RAR) > 3.5 indicate renal artery stenosis > 60%.12 It is also reported that a PSV > 200 cm/sec by ultrasonography is almost equal to a translesional pressure gradient > 20 mmHg by angiography.13 In cases of a resistive index (RI) > 0.8, renal parenchymal dysfunction is estimated to be severe. Our patient’s plasma renin activity (PRA) and serum aldosterone level were high, but duplex ultrasonography of the renal arteries did not reveal renal artery stenosis (Table 1). Given this information and the atrophic finding in both kidneys, we hesitated to perform further studies. However, accelerated renal dysfunction, congestion (flush pulmonary edema) and hypertension that required HD led us to perform CTA (Figure 2). In terms of treatment for renal artery stenosis, it is reported that angiotensin-converting enzyme inhibitors (ACE I) or angiotensin II receptor-blockers (ARBs) are effective in treating hypertension for 86–92% of patients.14 Caution should be practiced because ACEIs or ARBs can cause the progression of renal dysfunction,15 which was the case in our patient. Those agents are also contraindicated in cases of bilateral stenosis or functional unilateral stenosis. The indication for PTRA for ARAS is stated in the ACC/AHA 2005 guidelines.4 These guidelines cite the following: “...percutaneous revascularization is reasonable for patients with hemodynamically significant RAS and accelerated hypertension, resistant hypertension, malignant hypertension, hypertension with an unexplained unilateral small kidney, and hypertension with intolerance to medication (Class IIa, LOB B), percutaneous revascularization is indicated for patients with hemodynamically significant RAS and recurrent, unexplained congestive heart failure or sudden, unexplained pulmonary edema (Class I, LOB B).”4 Van et al reported that in the treatment of ostial ARAS, the primary success rate employing PTRA with or without stenting was 88% and 57%, respectively, and that the restenosis rate after a successful primary procedure in patients who underwent PTRA with or without stenting was in 14% and 48%, respectively. The author concluded that PTRA with stenting is a better approach in the treatment of ostial ARAS.16 However, concerning the recovery of renal function, it is still controversial.5 The resistive index (RI) has been said to predict the outcome in patients with renal artery stenosis who are undergo intervention. It is reported that among patients with renal artery stenosis > 50% of the luminal diameter and who underwent PTRA or surgery, a RI of at least 0.8 reliably identifies those who will not experience improved renal function.17 On the contrary, it is also reported that among patients with ARAS > 70% of the luminal diameter, even if the RI is > 0.8, PTRA with stenting offers favorable acute and long-term clinical results for the preservation of renal function.18 RI is currently controversial, with no reliable data on outcomes in patients with renal artery stenosis treated with PTRA. There is no evidence (such as randomized, controlled studies) that dilating a totally occluded renal artery is beneficial. However, recanalization of chronic total occlusions (CTOs) has been shown to be feasible in the coronary circulation.19 It is also reported that renal function was improved after opening a totally occluded renal artery with PTRA followed by stenting.20,21 In our case, severe and even occluded ostial ARAS was treated by stent placement, leading to recovery of the kidneys’ size, immediate satisfactory urination, and a normalized creatinine level and discontinuation of HD. At day-23 (8 days post intervention), a renogram showed that the right kidney functioned at nearly half the capacity as the left kidney (Figures 4A and B), which would imply that opening the right occluded renal artery contributed to the improvement of renal function to some extent. Our case provides new information regarding PTRA for ARAS and renal function prognosis due to this interventional approach. In our patient, the conditions implying negative indications and poor prognosis included: 1) small kidneys that looked atrophied and highly-echoic by ultrasound; 2) duplex ultrasonography did not show positive stenotic findings; 3) risk of contrast nephropathy; 4) total occlusion of the right renal artery.  Conditions implying a favorable prognosis for our patient included: 1) acute process of renal functional decline; 2) HD was initiated, which meant no further progression of azotemia and congestion; 3) the guidewire was able to reach the totally occluded renal artery which was probably suspected of recent occlusion; 4) immediate recovery of our patient’s kidney size and urine output. Our case thus provided several insights: 1) an atrophic high-echoic appearance of the kidney does not always mean irreversible function; 2) duplex ultrasonography and the RI do not always provide the right information; 3) an acute process of renal dysfunction with ARAS should be treated as quickly as possible; 4) even a totally occluded artery can be treated with PTRA when the guidewire can cross the occlusion. Acknowledgments. We wish to thank Jun-ichi Tasaki, Noriyuki Iehara, Takeshi Matsubara, Akira Mima, Misa Tanaka and Yoshinori Tanaka for consultation on the work-up and treatment of the patient.

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